A number sign (#) is used with this entry because of evidence that sarcoplasmic body myopathy (MYOSB), also known as myoglobinopathy, is caused by heterozygous mutation in the MB gene (160000) on chromosome 22q11.
Sarcoplasmic body myopathy (MYOSB), also known as myoglobinopathy, is an autosomal dominant disorder characterized by adult-onset muscle weakness affecting the proximal and distal muscles. Affected individuals usually present with proximal and axial muscle weakness leading to gait disturbances, although some present with hand muscle weakness and atrophy. The disorder is slowly progressive, and patients may lose ambulation after a long disease course. Some individuals develop respiratory or cardiac symptoms, often needing nocturnal ventilation. Other more variable features may include neck muscle weakness and dysphagia; facial muscle weakness is uncommon (Olive et al., 2019;Hama et al., 2022).
Edstrom et al. (1980) reported a large Swedish family in which 4 sibs had an adult-onset myopathy characterized by the onset of hand muscle weakness and atrophy between 39 and 43 years of age that progressed to involve the proximal muscles of the lower and upper limbs. Three of the patients became wheelchair-bound within about 10 years. There was little involvement of the neck and facial muscles. Some patients showed evidence of a cardiomyopathy and 1 had decreased respiratory functional vital capacity. EMG showed a myopathic pattern and serum creatine kinase was moderately elevated. Skeletal muscle biopsy showed sarcoplasmic bodies and an abundance of intermediate-sized filaments.Engvall et al. (2005) reported follow-up of the Swedish family reported byEdstrom et al. (1980) and identified another branch of this family with the disorder; none of the patients from the original report were still alive. Of 9 adults studied byEngvall et al. (2005), 5 had signs or symptoms of muscle weakness mainly affecting the hip flexor muscles. Two became wheelchair-bound 15 and 7 years after symptom onset. Muscle atrophy and weakness affected distal, proximal, and axial muscles. Facial muscles were not affected, but 2 patients with more severe disease showed mild respiratory muscle involvement with slightly decreased functional vital capacity. Two patients showed ECG abnormalities. Serum creatine kinase was elevated in most individuals, and muscle biopsies showed myopathic features with numerous sarcoplasmic bodies. There were a few clinically asymptomatic family members with increased serum creatine kinase or sarcoplasmic bodies, suggesting an early subclinical phase of the disease. In affected members of the family reported byEdstrom et al. (1980) andEngvall et al. (2005),Olive et al. (2019) identified a heterozygous missense mutation in the MB gene (H98Y;160000.0001).
Olive et al. (2019) reported 14 individuals from 6 unrelated European families, including the family (F3) with 6 affected individuals originally reported byEdstrom et al. (1980), with MYOSB associated with the heterozygous H98Y mutation in the MB gene. The families were identified by the characteristic presence of sarcoplasmic bodies in both type 1 and type 2 fibers on skeletal muscle biopsy. Overall, the patients had symptom onset between 33 and 49 years of age, presenting with weakness of the proximal lower limbs, pelvic girdle, and axial muscles, causing difficulties climbing stairs and rising from the floor. Distal hand weakness was the presenting sign in some patients from family F3. The disorder slowly progressed to involve distal leg and hand muscles, proximal muscles of the upper limb, and neck muscles. Five patients had dysphagia; none had facial involvement. Most patients developed respiratory failure requiring nocturnal noninvasive ventilatory support 10 years after disease onset and became wheelchair-dependent 15 to 20 years after onset. Cardiac involvement was observed in 6 patients. Family history revealed similarly affected individuals in families F1, F2, F3, and F4, whereas the patients in F5 and F6 had no family history. Six patients died of respiratory and/or cardiac failure between 18 and 30 years after disease onset. Serum creatine kinase was elevated and EMG showed myopathic features. Sarcoplasmic bodies were present in both skeletal and postmortem cardiac muscle.
Hama et al. (2022) reported a 75-year-old Asian woman with MYOSB. She first noted gait disturbances at age 55 and was unable to stand at age 64. The disorder was progressive; she developed distal muscle weakness with loss of ambulation at age 71. There was atrophy of the distal hand muscles and proximal muscles of the upper and lower limbs. She had progressive respiratory involvement with decreased forced vital capacity requiring nocturnal ventilation, as well as cardiac involvement with a reduced ejection fraction. Other features included dysarthria and dysphagia eventually requiring a feeding tube, notable weakness of the orbicularis oris muscle, and tongue weakness and atrophy, indicating facial involvement. Deep tendon reflexes were decreased and serum creatine kinase was elevated. Genetic analysis identified heterozygosity for the recurrent H98Y mutation in the MB gene.
The transmission pattern of MYOSB in the family reported byEdstrom et al. (1980) was consistent with autosomal dominant inheritance.
In affected members of 6 unrelated families of European descent with MYOSB,Olive et al. (2019) identified a heterozygous missense mutation in the MB gene (H98Y;160000.0001). The mutation in the families was found through different methods, including whole-exome sequencing (F1 and F2), linkage analysis and candidate gene sequencing (F3), and direct sequencing of the MB gene (F4, F5, and F6). The mutation was confirmed by Sanger sequencing and segregated with the disorder in all families. It was not present in public databases, including gnomAD. F3 had previously been reported byEdstrom et al. (1980). Haplotype analysis did not reveal a founder effect, suggesting that this is a recurrent mutation. Biochemical characterization indicated that the mutant myoglobin has altered O2 binding, exhibits a faster heme dissociation rate, and has a lower reduction potential compared to wildtype. Patient muscle biopsy samples showed evidence of lipid oxidation, increased intracellular superoxide, and increased sulfur content within sarcoplasmic bodies.
In a 75-year-old Asian woman with MYOSB,Hama et al. (2022) identified heterozygosity for the recurrent H98Y mutation in the MB gene. The mutation was found by whole-exome sequencing. Functional studies were not performed.
Edstrom, L., Thornell, L.-E., Eriksson, A.A new type of hereditary distal myopathy with characteristic sarcoplasmic bodies and intermediate (skeletin) filaments. J. Neurol. Sci. 47: 171-190, 1980. [PubMed:6251174,related citations] [Full Text]
Engvall, M., Ahlberg, G., Hedberg, B., Edstrom, L., Ansved, T.Sarcoplasmic body myopathy--a rare hereditary myopathy with characteristic inclusions. Acta Neurol. Scand. 112: 223-227, 2005. [PubMed:16146490,related citations] [Full Text]
Hama, Y., Mori-Yoshimura, M., Aizawa, K., Oya, Y., Nakamura, H., Inoue, M., Iida, A., Sato, N., Nonaka, I., Nishino, I., Takahashi, Y.Myoglobinopathy affecting facial and oropharyngeal muscles. Neuromusc. Disord. 32: 516-520, 2022. [PubMed:35527200,related citations] [Full Text]
Olive, M., Engvall, M., Ravenscroft, G., Cabrera-Serrano, M., Jiao, H., Bortolotti, C. A., Pignataro, M., Lambrughi, M., Jiang, H., Forrest, A. R. R., Benseny-Cases, N., Hofbauer, S., and 32 others.Myoglobinopathy is an adult-onset autosomal dominant myopathy with characteristic sarcoplasmic inclusions. Nature Commun. 10: 1396, 2019. [PubMed:30918256,images,related citations] [Full Text]
Alternative titles; symbols
| Location | Phenotype | Phenotype MIM number | Inheritance | Phenotype mapping key | Gene/Locus | Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 22q12.3 | Myopathy, sarcoplasmic body | 620286 | Autosomal dominant | 3 | MB | 160000 |
A number sign (#) is used with this entry because of evidence that sarcoplasmic body myopathy (MYOSB), also known as myoglobinopathy, is caused by heterozygous mutation in the MB gene (160000) on chromosome 22q11.
Sarcoplasmic body myopathy (MYOSB), also known as myoglobinopathy, is an autosomal dominant disorder characterized by adult-onset muscle weakness affecting the proximal and distal muscles. Affected individuals usually present with proximal and axial muscle weakness leading to gait disturbances, although some present with hand muscle weakness and atrophy. The disorder is slowly progressive, and patients may lose ambulation after a long disease course. Some individuals develop respiratory or cardiac symptoms, often needing nocturnal ventilation. Other more variable features may include neck muscle weakness and dysphagia; facial muscle weakness is uncommon (Olive et al., 2019; Hama et al., 2022).
Edstrom et al. (1980) reported a large Swedish family in which 4 sibs had an adult-onset myopathy characterized by the onset of hand muscle weakness and atrophy between 39 and 43 years of age that progressed to involve the proximal muscles of the lower and upper limbs. Three of the patients became wheelchair-bound within about 10 years. There was little involvement of the neck and facial muscles. Some patients showed evidence of a cardiomyopathy and 1 had decreased respiratory functional vital capacity. EMG showed a myopathic pattern and serum creatine kinase was moderately elevated. Skeletal muscle biopsy showed sarcoplasmic bodies and an abundance of intermediate-sized filaments. Engvall et al. (2005) reported follow-up of the Swedish family reported by Edstrom et al. (1980) and identified another branch of this family with the disorder; none of the patients from the original report were still alive. Of 9 adults studied by Engvall et al. (2005), 5 had signs or symptoms of muscle weakness mainly affecting the hip flexor muscles. Two became wheelchair-bound 15 and 7 years after symptom onset. Muscle atrophy and weakness affected distal, proximal, and axial muscles. Facial muscles were not affected, but 2 patients with more severe disease showed mild respiratory muscle involvement with slightly decreased functional vital capacity. Two patients showed ECG abnormalities. Serum creatine kinase was elevated in most individuals, and muscle biopsies showed myopathic features with numerous sarcoplasmic bodies. There were a few clinically asymptomatic family members with increased serum creatine kinase or sarcoplasmic bodies, suggesting an early subclinical phase of the disease. In affected members of the family reported by Edstrom et al. (1980) and Engvall et al. (2005), Olive et al. (2019) identified a heterozygous missense mutation in the MB gene (H98Y; 160000.0001).
Olive et al. (2019) reported 14 individuals from 6 unrelated European families, including the family (F3) with 6 affected individuals originally reported by Edstrom et al. (1980), with MYOSB associated with the heterozygous H98Y mutation in the MB gene. The families were identified by the characteristic presence of sarcoplasmic bodies in both type 1 and type 2 fibers on skeletal muscle biopsy. Overall, the patients had symptom onset between 33 and 49 years of age, presenting with weakness of the proximal lower limbs, pelvic girdle, and axial muscles, causing difficulties climbing stairs and rising from the floor. Distal hand weakness was the presenting sign in some patients from family F3. The disorder slowly progressed to involve distal leg and hand muscles, proximal muscles of the upper limb, and neck muscles. Five patients had dysphagia; none had facial involvement. Most patients developed respiratory failure requiring nocturnal noninvasive ventilatory support 10 years after disease onset and became wheelchair-dependent 15 to 20 years after onset. Cardiac involvement was observed in 6 patients. Family history revealed similarly affected individuals in families F1, F2, F3, and F4, whereas the patients in F5 and F6 had no family history. Six patients died of respiratory and/or cardiac failure between 18 and 30 years after disease onset. Serum creatine kinase was elevated and EMG showed myopathic features. Sarcoplasmic bodies were present in both skeletal and postmortem cardiac muscle.
Hama et al. (2022) reported a 75-year-old Asian woman with MYOSB. She first noted gait disturbances at age 55 and was unable to stand at age 64. The disorder was progressive; she developed distal muscle weakness with loss of ambulation at age 71. There was atrophy of the distal hand muscles and proximal muscles of the upper and lower limbs. She had progressive respiratory involvement with decreased forced vital capacity requiring nocturnal ventilation, as well as cardiac involvement with a reduced ejection fraction. Other features included dysarthria and dysphagia eventually requiring a feeding tube, notable weakness of the orbicularis oris muscle, and tongue weakness and atrophy, indicating facial involvement. Deep tendon reflexes were decreased and serum creatine kinase was elevated. Genetic analysis identified heterozygosity for the recurrent H98Y mutation in the MB gene.
The transmission pattern of MYOSB in the family reported by Edstrom et al. (1980) was consistent with autosomal dominant inheritance.
In affected members of 6 unrelated families of European descent with MYOSB, Olive et al. (2019) identified a heterozygous missense mutation in the MB gene (H98Y; 160000.0001). The mutation in the families was found through different methods, including whole-exome sequencing (F1 and F2), linkage analysis and candidate gene sequencing (F3), and direct sequencing of the MB gene (F4, F5, and F6). The mutation was confirmed by Sanger sequencing and segregated with the disorder in all families. It was not present in public databases, including gnomAD. F3 had previously been reported by Edstrom et al. (1980). Haplotype analysis did not reveal a founder effect, suggesting that this is a recurrent mutation. Biochemical characterization indicated that the mutant myoglobin has altered O2 binding, exhibits a faster heme dissociation rate, and has a lower reduction potential compared to wildtype. Patient muscle biopsy samples showed evidence of lipid oxidation, increased intracellular superoxide, and increased sulfur content within sarcoplasmic bodies.
In a 75-year-old Asian woman with MYOSB, Hama et al. (2022) identified heterozygosity for the recurrent H98Y mutation in the MB gene. The mutation was found by whole-exome sequencing. Functional studies were not performed.
Edstrom, L., Thornell, L.-E., Eriksson, A.A new type of hereditary distal myopathy with characteristic sarcoplasmic bodies and intermediate (skeletin) filaments. J. Neurol. Sci. 47: 171-190, 1980. [PubMed: 6251174] [Full Text: https://doi.org/10.1016/0022-510x(80)90002-7]
Engvall, M., Ahlberg, G., Hedberg, B., Edstrom, L., Ansved, T.Sarcoplasmic body myopathy--a rare hereditary myopathy with characteristic inclusions. Acta Neurol. Scand. 112: 223-227, 2005. [PubMed: 16146490] [Full Text: https://doi.org/10.1111/j.1600-0404.2005.00475.x]
Hama, Y., Mori-Yoshimura, M., Aizawa, K., Oya, Y., Nakamura, H., Inoue, M., Iida, A., Sato, N., Nonaka, I., Nishino, I., Takahashi, Y.Myoglobinopathy affecting facial and oropharyngeal muscles. Neuromusc. Disord. 32: 516-520, 2022. [PubMed: 35527200] [Full Text: https://doi.org/10.1016/j.nmd.2022.02.010]
Olive, M., Engvall, M., Ravenscroft, G., Cabrera-Serrano, M., Jiao, H., Bortolotti, C. A., Pignataro, M., Lambrughi, M., Jiang, H., Forrest, A. R. R., Benseny-Cases, N., Hofbauer, S., and 32 others.Myoglobinopathy is an adult-onset autosomal dominant myopathy with characteristic sarcoplasmic inclusions. Nature Commun. 10: 1396, 2019. [PubMed: 30918256] [Full Text: https://doi.org/10.1038/s41467-019-09111-2]
Dear OMIM User,
To ensure long-term funding for the OMIM project, we have diversified our revenue stream. We are determined to keep this website freely accessible. Unfortunately, it is not free to produce. Expert curators review the literature and organize it to facilitate your work. Over 90% of the OMIM's operating expenses go to salary support for MD and PhD science writers and biocurators. Please join your colleagues by making a donation now and again in the future. Donations are an important component of our efforts to ensure long-term funding to provide you the information that you need at your fingertips.
Thank you in advance for your generous support,
Ada Hamosh, MD, MPH
Scientific Director, OMIM